Our studies to date have determined that human oogonial stem cells, while far less stable than their murine counterparts, can be successfully expanded and propagated in culture. This has allowed us to begin testing the potential tumorigenicity of these cells with the ultimate goal of comparing the DNA signature of the oogonial stem cell-derived tumors to that of primary human ovarian cancer. We have also successfully introduced in human oogonial stem cells genetic alterations commonly detected in ovarian cancer. We are now generating tumors from these altered oogonial stem cells and will compare the histologic features in the tumors formed from the modified oogonial stem cells to those of primary tumors collected from women diagnosed with serous ovarian cancer. Also of importance is the identification of Ddx4-positive cells in xenografts derived from primary human ovarian serous tumors. The biological significance of this apparent rare population is yet to be determined. We have designed and implemented initial studies to test the relative tumorigenicity of Ddx4-positive, CD133-positive and Ddx4 CD133 double positive fractions. Demonstrating that these highly specialized human oogonial stem cells have the capacity to form ovarian tumors would be a major paradigm shift.